Overview on Testing for HHV-6 infection

Nearly 100% of us are infected with HHV-6B by early childhood. Little is known about the prevalence of HHV-6A, which is believed to be acquired later in childhood. Both HHV-6 viruses are highly cell associated and can be detected in plasma only briefly during the initial infection or acute reactivation. Most reactivation occurs in transplant patients taking immunosuppressant drugs or individuals with immune deficiencies. Detection of HHV-6 DNA in plasma generally means the patient has an active infection.

It is important to note that a negative finding in the plasma does not rule out a localized active infection in an organ (e.g. uterus, brain, thyroid, liver). Persistent HHV-6 infections have been found in the liver, brain, lungs, heart tissue and uterus, with  no trace of HHV-6 DNA in the plasma. Quantitative testing on blood and tissues is preferred because it can differentiate between the very low levels occasionally found in healthy controls and high levels found in diseased tissues.

Over 95% of us have antibodies to HHV-6 A/B. The relevant question when testing for HHV-6 antibodies is not whether you have them, but rather, are they unusually elevated on an IFA test?  Unfortunately, may laboratories just use the less expensive ELISA test that was only designed to answer the question of whether the antibodies exist (so fairly useless for HHV-6 testing). At the time of this publication we are aware of only two laboratories in the USA that offer antibody testing by IFA methodology – Quest Diagnostics and ARUP Laboratories.

Physicians and patients need to be aware that there is a rare inherited form of infection known as  “chromosomally integrated HHV-6” (ciHHV-6). Individuals with this condition, which occurs in 1% of the population, have one copy of the viral genome integrated into the chromosome of every nucleated cell, and therefore test positive by PCR DNA, even when asymptomatic.